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T Dorval

Publications and source records attributed to T Dorval.

At least 37 records · Page 2Linked to original sources
PubMed1998

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients.

PURPOSE: In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS: Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox's regression, respectively. RESULTS: Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION: Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

Adult↗
PubMed1997

Phase II trial of doxorubicin, 5-fluorouracil, etoposide, and cisplatin in advanced or recurrent endometrial carcinoma.

We have previously reported an overall response rate of 41% and a median survival duration of 14 months in a series of 49 patients with metastatic or recurrent endometrial carcinoma treated by a combination of etoposide, 5-fluorouracil, and cisplatin. In order to increase response rate and survival duration, doxorubicin was added to this combination. From August 1992 to January 1996, 20 consecutive patients were treated with a monthly combination chemotherapy consisting of doxorubicin 30 mg/m2 i.v. Day 1, 5-fluorouracil 600 mg/m2 i.v. Days 1 to 3, etoposide 80 mg/m2 i.v. Days 1 to 3, and cisplatin 35 mg/m2 i.v. Days 1 to 3 (AFEP). All patients were evaluable for response and toxicity. Median age was 62 years (range 45-72). Two to eight cycles were delivered (median 5). Two of 20 patients had complete response and 7 of 20 had partial response. The objective response rate was 45% (CI 95%: 23-68%). The median survival duration was 17 months. The median progression-free survival was 8 months. Major toxic effect was myelosuppression: 75% of grade 3 and 4 leukopenia and 20% of grade 3 and 4 thrombocytopenia. Seven patients (35%) developed infection and 4 (20%) were hospitalized once or more for toxicity. These results indicate that AFEP is an effective combination therapy in metastatic endometrial carcinoma but its toxicity is unacceptable.

Adenocarcinoma↗
PubMed1997

Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy.

PURPOSE: Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS: Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS: Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION: The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.

Adult↗
PubMed1997

Characterization of soluble gp130 released by melanoma cell lines: A polyvalent antagonist of cytokines from the interleukin 6 family.

gp130 acts as a common transducing signal chain for all receptors belonging to the interleukin (IL)-6 receptor family. The IL-6-related cytokines [IL-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor, ciliary neurotrophic factor, and cardiotrophin] often modulate tumor phenotype and control the proliferation of many tumor cell lines. We demonstrate that melanoma cell lines release, in vitro and in vivo (when transplanted in nude mice), soluble gp130 (sgp130), a potential antagonist of cytokines from the IL-6 family. Biochemical analysis revealed that sgp130 derived from melanoma patients' sera or from culture supernatants of melanoma cell lines is a Mr 104,000 protein that resolved after deglycosylation as a Mr 58,000 protein. PCR and Northern blot analysis only identified one gp130 membrane mRNA, suggesting that the soluble form of gp130 is generated by proteolytic cleavage. OSM reproducibly increases sgp130 released by melanoma cell lines, whereas leukemia inhibitory factor stimulates the production of sgp130 in only one of three cell lines tested. This tumor-derived sgp130 is functional because it binds in solution to the IL-6-soluble IL-6 receptor (gp80) complex. Recombinant sgp130 inhibits the growth inhibitory activity of the IL-6-soluble IL-6 receptor complex and OSM on some melanoma cell lines. Therefore, this soluble gp130 represents a natural antagonist of cytokines from the IL-6 family.

Animals↗
PubMed1996

[Immunotherapy in the treatment of cancers].

The recent discovery of the molecular structure of tumor antigens expressed by melanoma cells has contributed to the development of therapeutic strategies aimed at stimulating anti-tumor immunity. The first clinical trials in patients with cancer involved systemic administration of interleukin 2 alone or in combination with alpha-interferon or other chemotherapy agents. Objective clinical responses were observed in 15 to 25% of the patients with melanomas or renal cell cancer. In order to improve these encouraging early results, different clinical protocols are being evaluated with the goal of increasing intra-tumoral concentrations of the administered cytokines. Better optimization of methods for immunizing against specific tumor antigens naturally leads to the transition from non-specific stimulation of the human immune system to tumor antigen specific immunotherapy.

Animals↗
PubMed1996

Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen.

BACKGROUND: This retrospective study evaluates the results of a regimen of high-dose intrathecal methotrexate and the prognostic factors for the response in patients with meningeal from breast carcinoma. METHODS: From 1979 to 1994, 68 breast carcinoma patients were diagnosed with meningeal carcinomatosis at a mean age of 52 years. All but two had previous metastatic involvement. The proportion of lobular and ductal carcinomas was balanced. Malignant cells were present in cerebrospinal fluid (CSF) samples from 61 patients, whereas the 7 remaining patients had increased CSF protein associated with computerized tomographic scan evidence of meningeal metastases. From 1989, 41 of the patients received a regimen of high-dose intrathecal methotrexate with systemic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily x 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours after each MTX injection. Systemic treatment and radiation therapy were usually associated. Patients treated before 1988 received intrathecal MTX in conventional doses (15 mg once a week). RESULTS: Clinical objective response, defined as a neurological improvement for at least one month, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantly higher compared with that of the group treated with the conventional doses (P = 0.03). Median survival was 14 weeks for patients treated with the HD-MTX+FA regimen, compared with 7 weeks for patients who received conventional doses of MTX (P = 0.01). Grade 3 or 4 neutropenia was the main toxicity that occurred in 16 16 patients (39%) treated with the HD-MTX+FA regimen, and in 7 patients (33%) treated with conventional doses of MTX. In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy; controlled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrathecal therapy (P < 0.02). Multivariate analysis was not performed because the sample size was too small. CONCLUSIONS: Although this study was retrospective, the intrathecal HD-MTX+FA regimen appears to be a more efficient strategy than conventional doses of MTX to induce neurologic improvement and perhaps better survival. It should be recommended in combination with systemic chemotherapy for selected patients with meningeal carcinomatosis from breast carcinoma who are likely to benefit from intensive therapy, i.e., patients with a CSF protein level less than 5 g/L and in whom systemic disease has been controlled.

Adult↗
PubMed1996

Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.

BACKGROUND: The clinicopathologic features of infiltrating lobular carcinoma (ILC), which represents 5% to 15% of all breast cancers, are still controversial. In particular, the high frequency of multicentric lesions has led to questioning of the effectiveness of conservative treatment for this type of cancer. By studying a large number of cases, we aimed to compare the clinicopathological features of ILC with those of nonlobular infiltrating carcinoma (NLIC) and to assess the advisability of conservative therapy in the management of ILC. METHODS: The population analyzed included 726 cases of ILC, 249 cases of mixed ILC/invasive ductal carcinoma (ILC/IDC), and 10,061 cases of NLIC. The age of patients, TNM status, estrogen- and progesterone-receptor status (ER, PR), and histologic grades of the 3 groups were compared. The follow-up was carried out on a subgroup of 5846 cases. RESULTS: At diagnosis, ILC tumors were found to be larger on average and were detected in patients older than those with NLIC, but the degree of lymph node involvement was lower in patients with ILC than in NLIC. In ILC, tumors are more frequently grade I and ER-positive than in NLIC. Multicentric lesions were not significantly more frequent in ILC than in NLIC. The overall survival, locoregional control, disease free interval, and metastatic spread rates were not different among the three groups neither by univariate nor multivariate analysis, but the pattern of metastatic dissemination was different. In 480 cases of ILC considered for conservation therapy, the local recurrence and overall survival rates were similar to those observed for IDC. CONCLUSIONS: Our analysis specifies the clinicopathological features of ILC and confirms that conservation therapy may be an appropriate treatment for this type of cancer.

Breast Neoplasms↗
PubMed1996

Treatment of advanced or recurrent endometrial carcinoma with combination of etoposide, cisplatin, and 5-fluorouracil: a phase II study.

Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16-213 80 mg/m2 i.v. Days 1-3, 5-fluorouracil (5-FU) 600 mg/m2 i.v. Days 1-3, and cisplatin 35 mg/m2 i.v. Days 1-3. The objective response rate was 41% (95% CI, 27-54%) with 14.3% complete responses. The median survival duration was 14 months. The median response duration was 12 months. The estimated median survival for responders was 20 months. Three patients are still free of disease 5 years after treatment. The major toxic effects were myelosuppression (less than 25% of grade III and IV leucopenia, and 14% grade III and IV thrombocytopenia). Grade III peripheral neuropathy was observed in five patients. Cisplatin administration had to be stopped due to renal toxicity in six patients. No treatment-related deaths occurred. The combination of etoposide, 5 fluorouracil, and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

Adenocarcinoma↗
PubMed1996

Phase II trial of decapeptyl (D-TRP-6), a potent luteinizing hormone-releasing hormone analogue in untreated advanced breast cancer.

Decapeptyl (D-TRP-6), a potent luteinizing hormone-releasing hormone analogue, was administered to 27 premenopausal women with advanced breast cancer; patients were known to have hormone receptor-positive tumors. An overall response rate of 70% was achieved (complete response = 18%, partial response = 52%), with a median time to progression for the whole patient population of 12 months. Toxicity of the schedule was restricted to hot flushes, and the use of a 4-week initial covering period of tamoxifen prevented any flare-up of disease activity from occurring.

Adult↗
PubMed1996

Predictors of clinical response to interleukin-2--based immunotherapy in melanoma patients: a French multiinstitutional study.

PURPOSE: Various parameters have been reported to be correlated with response to interleukin-2 (IL-2) therapy. A multiinstitutional study was performed to assess by multivariate analysis the predictive value of known clinical and biologic melanoma prognostic markers recorded before the onset of IL-2 therapy on the likelihood of objective clinical response. PATIENTS AND METHODS: Serum C-reactive protein (CRP), IL-6, and lactate dehydrogenase (LDH) levels were measured in 81 metastatic melanoma patients included in different IL-2-based regimens before the starting of IL-2-therapy. Clinically defined prognostic groups, i.e., patients with superficial or visceral metastases, were also analyzed for response correlates. Patients were evaluated for response to treatment 4 to 6 weeks after completion of one course of therapy. RESULTS: On univariate analysis, the pretreatment values of CRP (P = .001), IL-6 (P = .007), and LDH (P = .02) and site of metastases (P = .0004) were correlated with clinical response. However, only CRP (P < .007) and clinically defined group (P < .004) were independent predictors on multifactorial analysis. Indeed, when adjusted to CRP, IL-6 tended to improve patient selection, but did not reach statistical significance (P = .07). Furthermore, using multivariate survival analysis based on the Cox proportional hazards model, only CRP was found to be an independent prognostic factor for survival (P < .0001). CONCLUSION: In this study, patients with high serum levels of CRP and/or visceral organ involvement before therapy were unlikely to respond to IL-2 therapy. Therefore, clinical classification based on the site of metastases and serum CRP determination before the start of IL-2 therapy may help to improve selection of melanoma patients who may benefit from IL-2 and could prevent unnecessary morbidity.

Adult↗
PubMed1996

Protracted continuous infusion of 5-fluorouracil in combination with doxorubicin, vincristine, and oral cyclophosphamide in advanced breast cancer.

Several studies suggest that protracted continuous infusion constitutes an important way to optimize the dose and the efficacy of 5-fluorouracil (5-FU) in metastatic cancer. Eighty-three women aged 27-76 (median age 55) with metastatic breast cancer were treated every 4 weeks with a continuous ambulatory venous infusion of 5-FU 350 mg/m2/day and oral cyclophosphamide 100 mg/m2/day over 15 days. The continuous therapy was associated with a weekly administration of vincristine (0.8 mg/m2) and doxorubicin (15 mg/m2) on day 1, day 8, and day 15. Cycles were repeated every 28 days. Thirty-four patients were treated in first-line metastatic chemotherapy and 49 in second-line. Toxicities included: mucositis (grade > or = 2) 23%, diarrhea (grade > or = 2) 7%, a hand-foot syndrome (grade > or = 2) 9%, alopecia (grade 3) 21%, neurological (grade > or = 2) 4%, grade 3 and 4 leukopenia 29%, and grade 3 and 4 thrombopenia 8%. Heart toxicity was only 3%. Catheter infection was observed in 1 case and 7 patients experienced thrombosis. The overall objective response rate (OR) was 48% and the complete response rate was 23%. The median duration of response was 10 months. The median survival was 16 months. Activity was better in naive than pretreated women (respectively, 55% and 42% of OR, p = 0.21). Analysis of responses according to the metastatic sites shows the pronounced efficacy on soft tissue diseases (skin recurrences 42%, lymph nodes 52%), and also in visceral metastases (hepatic 36%, lung 34%).

Administration, Oral↗
PubMed1996

Ifosfamide seven-day infusion for recurrent and cisplatin refractory ovarian cancer.

BACKGROUND: The prognosis of advanced ovarian cancer is very poor, with about 15% of patients surviving at five years. Since most of these patients will relapse and/or progress while on therapy, effective salvage treatments are needed. A phase II trial was designed to evaluate the feasibility, toxicity, and response of a seven-day ambulatory continuous infusion of ifosfamide in patients with recurrent or chemoresistant advanced ovarian cancer. PATIENTS AND METHODS: Nineteen patients with progressive ovarian cancer following a cisplatin-based induction chemotherapy were treated with continuous infusion ifosfamide with mesna at 1 g/m2/d and 400 mg/m2/d, respectively, for seven days every 28 days. RESULTS: The overall response rate was 37%. Responses were observed both in patients who relapsed after induction chemotherapy (4/6) and in those who were resistant to cisplatin (3/13). Toxicity was mild and tolerable in these heavily pretreated patients. CONCLUSION: Ifosfamide, when administered as a protracted continuous infusion is an active drug in ovarian cancer and can be safely administered in an out-patient setting. Toxicity is minor even in heavily pretreated patients. Responses are observed in cisplatin refractory ovarian cancer.

Adult↗
PubMed1996

First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer.

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.

Adult↗